Evidence map›Paper›PMID 39909038›Full record

ArticleCell host & microbe2025

Rare twin cysteine residues in the HIV-1 envelope variable region 1 link to neutralization escape and breadth development.

Maria C Hesselman, Marius Zeeb, Peter Rusert, Chloé Pasin, Jennifer Mamrosh, Samuel Kariuki, Ian Pichler, Michèle Sickmann, Masako M Kaufmann, Daniel Schmidt and 28 more

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Article in Cell host & microbe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

38 authors.

Maria C HesselmanInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland.
Marius ZeebInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich (USZ), 8091 Zurich, Switzerland.
Peter RusertInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland.
Chloé PasinInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich (USZ), 8091 Zurich, Switzerland.
Jennifer MamroshTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Samuel KariukiDepartment of Biological Sciences, School of Science, University of Eldoret, 30100 Eldoret, Kenya; Institute for Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town and National Health Laboratory Service, 7925 Cape Town, South Africa.
Ian PichlerInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland.
Michèle SickmannInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland.
Masako M KaufmannInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland.
Daniel SchmidtInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland.
Nikolas FriedrichInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland.
Karin J MetznerInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich (USZ), 8091 Zurich, Switzerland.
Audrey RindlerInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich (USZ), 8091 Zurich, Switzerland.
Herbert KusterInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich (USZ), 8091 Zurich, Switzerland.
Craig AdamsInstitute for Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town and National Health Laboratory Service, 7925 Cape Town, South Africa.
Ruwayhida ThebusInstitute for Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town and National Health Laboratory Service, 7925 Cape Town, South Africa.
Michael HuberInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland.
Sabine YerlyLaboratory of Virology, University Hospital Geneva, University of Geneva, 1205 Geneva, Switzerland.
Karoline LeuzingerClinical Virology, University Hospital Basel, 4031 Basel, Switzerland.
Matthieu PerreauDivision of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, 1011 Lausanne, Switzerland.
Roger KollerInstitute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland.
Günter DollenmaierCentre for Laboratory Medicine, 9008 St. Gallen, Switzerland.
Simona FrigerioInstitute of Laboratory Medicine, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland.
Dylan H WestfallDepartment of Microbiology at the University of Washington, Seattle, WA 98195, USA.
Wenjie DengDepartment of Microbiology at the University of Washington, Seattle, WA 98195, USA.
Allan C deCampFred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Michal JuraskaFred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Srilatha EdupugantiDepartment of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA 30322, USA.
Nyaradzo MgodiUniversity of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe; University of California, San Francisco, San Francisco, CA 94115, USA.
Hugh MurrellInstitute for Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town and National Health Laboratory Service, 7925 Cape Town, South Africa.
Nigel GarrettDepartment of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, 4041 Durban, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, 4013 Durban, South Africa.
Kshitij WaghTheoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
James I MullinsDepartment of Microbiology at the University of Washington, Seattle, WA 98195, USA.
Carolyn WilliamsonInstitute for Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town and National Health Laboratory Service, 7925 Cape Town, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, 4013 Durban, South Africa.
Penny L MooreSA MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, 2050 Johannesburg, South Africa; National Institute for Communicable Disease of the National Health Laboratory Services, 2192 Johannesburg, South Africa; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, 4013 Durban, South Africa.
Huldrych F GünthardInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich (USZ), 8091 Zurich, Switzerland.
Roger D KouyosInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich (USZ), 8091 Zurich, Switzerland.
Alexandra TrkolaInstitute of Medical Virology, University of Zurich (UZH), 8057 Zurich, Switzerland. Electronic address: trkola.alexandra@virology.uzh.ch.

Funding

Bill & Melinda Gates Foundation INV-036842
6 · The paper itself

Abstract

Identifying HIV-1 envelope (Env) traits associated with neutralization cross-reactivity is crucial for vaccine design. Variable loops 1 and 2 (V1V2), positioned at the Env trimer apex, are key regions linked to neutralization. We describe non-canonical cysteine (Cys) residues in V1 that are enriched in individuals with elite neutralization breadth. Analyzing over 65,000 V1 sequences from the CATNAP database, AMP trials, and longitudinal HIV-1 cohorts (SHCS, ZPHI, and CAPRISA), we found that Env variants with extra V1 Cys are present at low levels and fluctuate over time. Extra V1 Cys associate with elite plasma neutralization, and two additional Cys are preferred, suggesting stabilization through disulfide bonds. Among 34 broadly neutralizing antibody (bnAb)-inducer Envs, 17.6% had elongated V1 regions with extra Cys. These extra Cys moderately increased neutralization resistance and altered bnAb epitope accessibility. Collectively, altering epitope exposure alongside Env stabilization renders the V1 twin Cys motif a promising feature for HIV-1 bnAb immunogens.

Indexed as

Antibodies, NeutralizingCysteineenv Gene Products, Human Immunodeficiency VirusHIV-1HIV AntibodiesHIV Envelope Protein gp120Cross ReactionsEpitopesHIV InfectionsHumansAntibodies, NeutralizingCysteineenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesHIV Envelope Protein gp120broadly neutralizing antibodieselite neutralizersenvelope glycoproteinEnv stabilizationHIV vaccineV1V2

Identifiers

PMID39909038
PMCPMC13621619

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